INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2020
·
IF 5.162
Dinglingge Cao,Huangjuan Li,Yuan Luo,Nianping Feng,Tianyuan Ci
Phototherapy holds promise in cancer treatment for its prominent antitumor efficacy and low systematic toxicity compared with traditional chemotherapy. However, the higher risk of tumor metastasis caused by the severe hypoxic state during phototherapy is a threat in practical use. Here, in order to tackle this challenge, we developed a delivery system via loading the photosensitizer indocyanine green (ICG) into the low molecular weight heparin (LMWH) modified liposomes (LMWH-ICG-Lip) to realize the synergistic effects between photosensitizer and drug vehicle, achieving better phototherapeutic efficacy and meanwhile alleviating the potential risk of tumor metastasis caused by phototherapy. In this system, besides elongating the photosensitizers' circulation time and enhancing their accumulating efficacy to tumor tissues, LMWH itself also exhibited anti-metastasis efficacy via inhibiting adhesion of platelets to tumor cells and decreasing migration and invasion capability of tumor cells. In vivo efficacy evaluation was conducted on orthotopic 4T1 breast cancer model, and the system of LMWH-ICG-Lip could alleviate metastasis potential of residual tumor cells after irradiation, and elicit optimistic antitumor and anti-metastasis efficacy for phototherapy.
研究领域:
肿瘤学
·
药学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Asian Journal of Pharmaceutical Sciences
·
2022
·
IF 9.273
Qiongzhe Ren,Xuefeng Tang,Yi Lu,Qing Li,Zhiqian Liao,Shinan Jiang,Haoli Zhang,Zhigang Xu,Lei Luo
The use of nanocrystal technology to manufacture drug delivery systems intended to enhance therapeutic efficacy has attracted the attention of the pharmaceutical industry. However, the clinical application of nanocrystal drugs for injection is restricted by Ostwald ripening and the large-scale use of stabilizers such as polysorbate and lecithin, which have potential toxicity risks including hemolysis and allergies. Here, we designed an amorphous nanocrystal drug complex (IHNC), which is stabilizer-free and composed of indocyanine green (ICG) framework loading with a chemotherapeutic agent of 10-hydroxycamptothecin (HCPT). Considering the possibility of industrial manufacturing, IHNC was simply prepared with the assistance of ferric ion (III) via supramolecular assembly strategy. The theoretical result of Materials Studio simulation indicated that the prepared ICG-Fe(III) framework showed a stable spherical structure with the appropriate cavity for encapsulating the two drugs of HCPT and ICG with equal mass ratio. The IHNC was stable at physiological pH, with excellent PTT/PDT efficacy, and in vivo probing characteristics. The nanoscale size and reductive stimuli-responsiveness can be conducive to drug accumulation into the tumor site and rapid unloading of cargo. Moreover, such combination therapy showed synergistic photo/chemotherapy effect against 4T1 breast cancer and its tumor inhibition rate even up to 79.4%. These findings demonstrated that the nanocrystal drug delivery strategy could avoid the use of stabilizers and provide a new strategy for drug delivery for combination therapy.
研究领域:
药学
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肿瘤学
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纳米医学
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产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2024
·
IF 2.5
Lin Zhan,Xuelian Yin,Li Qiu,Chenchen Li,Yanli Wang
The nanomedicine system based on dual drug delivery systems (DDDs) can significantly enhance the efficacy of tumor treatment. Herein, a metal-organic framework, Zeolite imidazole salt frames 8 (ZIF-8), was successfully utilized as a carrier to load the dual chemotherapeutic drugs doxorubicin (DOX) and camptothecin (CPT), named DOX/CPT@ZIF-8 (denoted as DCZ), and their inhibitory effects on 4T1 breast cancer cells were evaluated. The study experimentally demonstrated the synergistic effects of the dual chemotherapeutic drugs within the ZIF-8 carrier and showed that the ZIF-8 nano-carrier loaded with the dual drugs exhibited stronger cytotoxicity and inhibitory effects on 4T1 breast cancer cells compared to single-drug treatment. The use of a ZIF-8-based dual chemotherapeutic drug carrier system highlighted its potential advantages in suppressing 4T1 breast cancer cells.
研究领域:
纳米医学
·
肿瘤学
·
药物递送
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DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2025
·
IF 6.5
Xiaoyan Yuan,Yunfeng Bi,Ji Liu,Wenhao Xu,Mingjuan Li,Kexin Li,Yan Zou,Xing Wang,Yanqing Chen,Qiming Yang
Objective Andrographolide (AG) demonstrated promising anticancer efficacy against the initiation and progression of breast cancer by triggering the mitochondria-mediated intrinsic apoptotic pathway. However, its clinical translation is still hindered by drawbacks such as poor bioavailability and off-target effects; therefore, an optimized drug-delivery system that minimizes these effects is urgently needed. To address these issues, we successfully developed a mitochondria-targeting nanocarrier (TPP-PEG-PCL) with high drug-loading capacity and excellent biocompatibility.Methods The mitochondria-targeting copolymer (TPP-PEG-PCL) was synthesized chemically and used to prepare AG-loaded polymeric micelles (TPP-PEG-PCL@AG) by solvent-evaporation method. In vitro, the blank micelles were first evaluated for biocompatibility with mouse breast-cancer cells (4T1) and endothelial cells (EC). Subsequently, a panel of cellular assays was performed on 4T1 cells to compare the antitumor activity of free AG, PEG-PCL@AG, and TPP-PEG-PCL@AG, confirming the enhanced cancer-cell killing achieved through mitochondria-targeted delivery of AG.Results The results showed that TPP-PEG-PCL micelles were readily taken up by 4T1 cells and selectively accumulated in mitochondria with a Pearson’s correlation (Rr) 0.47 compared to 0.25 in PEG-PCL micelles group, leading to a pronounced inhibition of proliferation and migration. By elevating intracellular ROS, decreasing mitochondrial membrane potential, and activating the caspase cascade, the micelles induced apoptosis and thereby achieved mitochondria-targeted potentiation of TPP-PEG-PCL@AG. However, this study is limited to in vitro validation using the 4T1 murine model, and further in vivo investigations are warranted to assess translational efficacy and potential systemic toxicity..Conclusion PCL-PEG nanoparticles decorated with TPP combine pronounced mitochondria-targeting specificity, high drug-loading capacity, excellent biocompatibility and readily tunable architecture, making them an ideal platform for constructing a precise mitochondrial-intervention system for AG. This strategy is particularly attractive for tumor-targeted delivery of AG and opens a new avenue for its clinical translation.
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOSCIENCE AND NANOTECHNOLOGY
·
2015
·Vol. 15
·期 6
·4111-4118
·
IF 1.556
Song Lina,Zang Fengchao,Song Mengjie,Chen Gong,Zhang Yu,Gu. Ning
In this strategy, a magnetic fluid of the Fe3O4 nanomicelles was synthesized with amphiphilic PEGylated phospholipid as surfactant and soybean oil as stabilizer under simple mechanical stirring and subsequent ultrasonication. Transmission electron microscope (TEM)
measurement indicated that the sample is monodisperse spherical Fe3O4 nanoparticles with internal core size of 9 nm and external nanomicelle shell thickness of 1.5 nm. The final hydrodynamic size of the sample is 19.5 nm and its zeta potential is −38.5 mV, suggesting
good stability of the magnetic nanomicelles in water. To assess the ability of magnetic nanomicelles to escape reticuloendothelial system (RES) uptake, in vitro cell phagocytosis experiments were conducted using murine macrophages (RAW264.7). The results indicated that the PEGylation
can effectively prevent the uptake of the nanomicelles by the macrophages. Using a mouse model of 4T1 breast cancer, the nanomicelles provided a good magnetic resonance imaging (MRI) capability to sensitively detect tumor by enhanced permeability and retention (EPR) effect. The PEGylated monodisperse
magnetic nanomicelles would become a potential contrast agent for passive targeting diagnosis of tumor by MR imaging.
研究领域:
纳米技术
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医学成像
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癌症研究
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材料科学
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DOI
PubMed
高影响因子
MEDICINAL CHEMISTRY RESEARCH
·
2022
·Vol. 31
·期 4
·605-616
·
IF 2.351
Shi Jing-Fang,Wu Ping,Li Han-Xiang,Wei Xiao-Yi,Jiang Zi-Hua
Annonaceous acetogenins are potent ubiquinone-linked NADH oxidase inhibitors and have potent anticancer activity. Their usage in the clinic is limited because of their significant toxicity to normal cells. To obtain novel low toxicity antitumoral prodrugs, squamocin and bullatacin were covalently linked to N -butoxycarbonyl protected glycine-proline dipeptide (Boc-Gly-Pro), which may be recognized and cleaved by fibroblast activation protein (FAP), a serine protease overexpressed on the surface of tumor-associated fibroblasts. Ten squamocin and bullatacin derivatives were synthesized by attaching Boc-Gly-Pro either directly or through 6-aminocaproic acid linker to a hydroxyl group of squamocin or bullatacin. All derivatives showed high potency to inhibit 4T1 breast cancer cell line growth in the sub-µM to µM range. Compound 8 was the most active (IC 50 0.30 μM) and displayed higher activity than squamocin. Most derivatives, however, display reduced potency by up to 50 folds compared to the parent drug. In the presence of FAP enzyme, the anticancer potency of compound 3 against A549, HeLa, HepG2 and MCF-7 cells was increased by up to eight folds. The data suggest that Boc-Gly-Pro-acetogenin prodrugs may show improved therapeutic potential of these acetogenins by reducing the drug doses and the toxic side effects.
Graphical abstract
研究领域:
药理学
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肿瘤学
·
药物化学
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产品关联
DOI
高影响因子
RSC Advances
·
2023
·Vol. 13
·期 9
·5609-5618
·
IF 3.9
Wen Kang,Yuyuan Shi,Zhenlu Yang,Xindao Yin,Ying Zhao,Lixing Weng,Zhaogang Teng
As a non-invasive cancer treatment, photodynamic therapy (PDT) has great applications in superficial tumors because of its high selectivity and low cumulative toxicity. However, the poor tumor-targeting ability and short blood circulation time of conventional photosensitizers (PSs) limit the efficacy of PDT to some extent. In this study, we synthesized flexible hollow human serum albumin (HHSA) and loaded photosensitizer Chlorin e6 (Ce6) and the chemotherapeutic drug Doxorubicin (DOX) for synergistic cancer therapy. HHSA can enhance drug delivery and cellular uptake through targeting gp60 and SPARC receptors and unique flexible hollow structures. The TEM images show that HHSA possesses distinct flexible hollow structures, as well as good monodispersity and deformability. After loading Ce6 and DOX, HHSA@Ce6-DOX displays better therapeutic effects than HHSA@DOX on the growth of 4T1 breast cancers without irradiation. Remarkably, it has a significantly higher therapeutic effect (relative cell activity: 45% vs. 74%) than HHSA@Ce6 under 660 nm irradiation. Furthermore, the excellent biocompatibility of HHSA@Ce6-DOX has been proved both in vitro and in vivo, indicating that it has a promising future in synergistic tumor treatments.
研究领域:
药学
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纳米技术
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癌症研究
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Nanoscale
·
2019
·Vol. 12
·期 3
·1801-1810
·
IF 6.97
Yang Gao,Luyun Zhang,Yanhong Liu,Sijia Sun,Zhibin Yin,Lili Zhang,Aiguo Li,Guangming Lu,Aiguo Wu,Leyong Zeng
Black titanium dioxide (TiO2) nanoparticles have attracted great attention due to their application in photothermal therapy (PTT). However, single-mode phototherapy has the risk of recurrence, and the high-dose laser usually imposed to improve the PTT performance can bring a potential threat to security. Here, polydopamine (PDA)-coated black TiO2 (b-P25@PDA) nanoparticles with a core–shell structure were synthesized for enhanced PTT; then, synergistic phototherapy nanoprobes (b-P25@PDA-Ce6 (Mn)) were constructed by coupling chlorin e6 (Ce6) and chelating Mn2+ for simultaneous photodynamic therapy (PDT)/PTT and magnetic resonance (MR) imaging, in which a low-dose laser was used and imaging-guided phototherapy with high efficiency and high safety was achieved. The prepared nanoprobes showed high photothermal conversion efficiency (32.12%), high reactive oxygen generation and excellent MR imaging. In the 4T1 tumor-bearing nude mouse model, the tumors completely disappeared under the combination of PDT/PTT with a low-dose laser but were only partially inhibited by single PDT and single PTT. The current work developed a multifunctional black TiO2-based nanoprobe for enhanced synergistic PDT/PTT and MR imaging, which will be important for the safe and efficient visualized theranostics of cancers.
研究领域:
纳米技术
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癌症治疗
·
生物医学工程
·
材料科学
·
医学成像
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产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2023
·
IF 17.1
Lifeng Luo,Baoli Zhang,Feng Tao,Zhong Chen,Qingsong Ye,Xiaozhi Zhao,Jinhui Wu
Tumor metastasis contributes to the low overall survival of tumor patients, while transforming growth factor-β (TGFβ) has been recognized as a prominently promoting factor in the development of tumor metastasis. Platelets reserve abundant TGFβ, which will be secreted to peripheral blood after activation, and they are the dominant source of circulating TGFβ. Therefore, downregulation of platelet-derived TGFβ is expected to inhibit the metastasis of circulating tumor cells. Here, unfolded human serum albumin (HSA)-coated perfluorotributylamine (PFTBA) nanoparticles were constructed to display a favorable platelet delivery and an antiplatelet effect to downregulate platelet-derived TGFβ in vitro and in blood plasma. PFTBA@HSA-mediated TGFβ downregulation impaired epithelial-mesenchymal transition of tumor cells as well as their migration and invasion behaviors and enhanced immune surveillance of NK cells. Intravenous injection of PFTBA@HSA effectively reduced tumor metastasis on the lungs or liver to improve the survival rate of mice on multiple metastatic models, including CT26 colon cancer, B16F10 melanoma, and 4T1 breast cancer. Compared with the clinical antiplatelet drug ticagrelor, PFTBA@HSA reduced bleeding risk when displaying a favorable downregulation on platelet-derived TGFβ, thereby obtaining a higher therapy benefit. Together, this study confirmed that downregulation of platelet-derived TGFβ by PFTBA@HSA will be a potential approach and therapeutic candidate for the prevention of tumor metastasis.
研究领域:
肿瘤学
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药理学
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纳米技术
·
免疫学
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DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2021
·
IF 9.776
Mengshi Jiang,Bing Qin,Lihua Luo,Xiang Li,Yingying Shi,Junlei Zhang,Zhenyu Luo,Chunqi Zhu,Guannan Guan,Yongzhong Du,Jian You
The hypoxic tumor microenvironment (TME) hinders the effectiveness of immunotherapy . Alleviating tumor hypoxia to improve the efficacy of immune checkpoint inhibitors (ICIs) represented by programmed cell death protein 1 (PD-1) antibody has become a meaningful strategy. In this study, we adopted three methods to alleviate hypoxia, including direct oxygen delivery using two different carriers and an indirect way involving HIF-1α inhibition. Both in vivo and in vitro experiments showed that liposomes modified with perfluorocarbon or hemoglobin ( [email protected] or [email protected] ) were able to efficiently load and release oxygen, relieving tumor hypoxia. However, the gas release behavior of [email protected] was uncontrollable, which might induce acute hyperoxia side effects during intravenous injection and reduce its biosafety. In contrast, whether administered locally or systemically, [email protected] revealed high animal tolerance, and was much safer than commercial HIF-1α inhibitor (PX-478), displaying prospects as a promising oxygen carrier for clinical practice. Pharmacodynamic experiments suggested that [email protected] helped PD-1 antibody break the therapeutic bottleneck and significantly inhibited the progression of 4 T1 breast cancer. But in CT26 colon cancer , the combination therapy failed to suppress tumor growth. After in-depth analysis and comparison, we found that the ratio of M1/M2 tumor associated macrophages (TAMs) between these two tumor models were dramatically different. And the lower M1/M2 ratio in CT26 tumors limited the anti-tumor effect of combination therapy. In this study, three methods for alleviating tumor hypoxia were compared from the perspectives of biosafety, efficacy and clinical applicability. Among them, [email protected] stood out, and its combined use with PD-1 antibody exhibit a distinct synergistic suppression effect on tumors with more M1 macrophages presented in the microenvironment. Our work provided a good reference for improving the efficacy of PD-1 antibody by alleviating tumor hypoxia.
研究领域:
肿瘤学
·
免疫疗法
·
药理学
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
MATERIALS & DESIGN
·
2022
·
IF 9.417
Yuqin Yang,Desheng Cai,Yisong Shu,Zhihua Yuan,Wenmin Pi,Yaozhi Zhang,Jihui Lu,Jingyi Jiao,Xuehao Cheng,Feifei Li,Penglong Wang,Haimin Lei
It is crucial to inhibit tumor growth and distant metastasis for breast cancer (BC) therapy. However, the treatment primarily dependent on surgery, chemotherapy, and radiotherapy is far from satisfactory. It had been demonstrated that the CXCL1/2-S100A8/9 axis played an essential role in BC therapy. Therefore, we constructed a natural product hydrogel for BC therapy by blocking CXCL1 signaling. The GK-GA (phytochemicals of Genkwa Flos -glycyrrhizic acid) hydrogel was designed in a one-step “green” approach. The pharmacodynamics study showed GK-GA exhibited significant anti-tumor and anti-lung metastasis activities, resulting in the inhibition rate of tumor growth (IRG) over 90 % at 6.25 mg·kg −1 , and did not display any obvious toxicity. In addition, the potent antitumor efficiency was also attributed to aggregation/assembly-induced retention (AIR) property. RNA sequencing analysis revealed the gene expression was significantly down-regulated in the GK-GA group, which were BCL2, CASP3, CXCL1, CXCL2, CXCR2, S100A8, S100A9, and confirmed further by western blot (WB). Our findings indicated natural product GK-GA hydrogel inhibited tumor growth and lung metastasis via the BCL2-CASP3 mitochondrial apoptosis pathway as well as the CXCL1/2-S100A8/9 pathway. This study provides inspiration for the fabrication of new excipients-free nano-dispersion in a one-step, no‐carrier‐added, organic solvent-free, “green” approach, particularly for small molecular antitumor agents.
研究领域:
肿瘤学
·
药学
·
分子生物学
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癌症治疗
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产品关联
DOI
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2023
·
IF 9.9
Yunchao Zhao,Tian Huang,Shaobo Wang,Shuncheng Yao,Quanhong Hu,Xingyi Wan,Ning Guo,Yang Zhang,Linlin Li
Sonodynamic therapy (SDT) is considered as a new-rising strategy for cancer therapeutics, but the inefficient production of reactive oxygen species (ROS) by current sonosensitizers seriously hinders its further applications. Herein, a piezoelectric nanoplatform is fabricated for enhancing SDT against cancer, in which manganese oxide (MnO x ) with multiple enzyme-like activities is loaded on the surface of piezoelectric bismuth oxychloride nanosheets (BiOCl NSs) to form a heterojunction . When exposed to ultrasound (US) irradiation, piezotronic effect can remarkably promote the separation and transport of US-induced free charges, and further enhance ROS generation in SDT. Meanwhile, the nanoplatform shows multiple enzyme-like activities from MnO x , which can not only downregulate the intracellular glutathione (GSH) level, but also disintegrate endogenous hydrogen peroxide (H 2 O 2 ) to generate oxygen (O 2 ) and hydroxyl radicals (•OH). As a result, the anticancer nanoplatform substantially boosts ROS generation and reverses tumor hypoxia . Ultimately, it reveals remarkable biocompatibility and tumor suppression in a murine model of 4 T1 breast cancer under US irradiation. This work provides a feasible pathway for improving SDT using piezoelectric platforms.
研究领域:
纳米技术
·
癌症治疗
·
材料科学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）